It has been shown that intravenous fatty acids given to normal volunteers in the form of heparin and lipid emulsions will cause insulin resistance in a matter of a few hours. It is not known if this same phenomenon can be demonstrated with oral fat. The investigators are specifically interested in whether or not there are differences in the induction of insulin resistance between the 3 main classes of fatty acids (saturated, monounsaturated and polyunsaturated).

The investigators also plan to evaluate endothelial dysfunction and blood pressure; both of which frequently accompany insulin resistance.

Change in Insulin Sensitivity from Baseline at Two Weeks [ Time Frame: Average of 2 weeks. ] [ Designated as safety issue: No ]

Insulin sensitivity will be measured twice (once at baseline following a nasoduodenal infusion of saline for 6 hours; two weeks later following a nasoduodenal infusion of a vegetable oil high in one of 3 fatty acids for 6 hours) using a euglycemic, hyperinsulinemic clamp as described by R. DeFronzo. The actual measurement is expressed as a glucose infusion rate.

Secondary Outcome Measures:

Change in Endothelial Function from Baseline at Two Weeks [ Time Frame: Average of two weeks ] [ Designated as safety issue: No ]

Endothelial function will be measured by measuring the dilation of the brachial artery in the elbow following occlusion by a blood pressure cuff, which is then released. The actual measurement involves use of ultrasound by an investigator experienced with this technique.

Change in Systolic Blood Pressure at Two Weeks [ Time Frame: Average of two weeks ] [ Designated as safety issue: No ]

Blood pressure will be measured using a standard automated blood pressure cuff. The measurements will be taken several times during each study day.

On the study day, each participant will receive 100 grams of a randomly assigned fat via a nasoduodenal tube. The oil will be infused at a rate of ~1 tablespoon per hour so that the total infusion time will be 6 hours.

Active Comparator: Monounsaturated fat

Olive oil (rich in the monounsaturated fat oleate)

Other: Dietary fat

On the study day, each participant will receive 100 grams of a randomly assigned fat via a nasoduodenal tube. The oil will be infused at a rate of ~1 tablespoon per hour so that the total infusion time will be 6 hours.

Active Comparator: Polyunsaturated fat

Safflower oil (rich in the polyunsaturated fat linoleate)

Other: Dietary fat

On the study day, each participant will receive 100 grams of a randomly assigned fat via a nasoduodenal tube. The oil will be infused at a rate of ~1 tablespoon per hour so that the total infusion time will be 6 hours.

Detailed Description:

Type 2 Diabetes and cardiovascular disease are closely linked. A common abnormality in both conditions is insulin resistance. The primary cause of insulin resistance in not known. A significant question is what dietary components contribute to the development of insulin resistance. Based on epidemiologic data, it seems that the type of dietary fat is a significant contributor to the development of insulin resistance. However, some researchers argue that the main determinant is total amount of fat, not the composition.

This study is intended to determine if the main types of fat (saturated, monounsaturated and polyunsaturated) ingested over a short time can cause insulin resistance in lean, healthy people. It has been demonstrated that 6 hours of intravenous fat infused into lean, healthy subjects can result in insulin resistance, as well as blood pressure elevation and endothelial dysfunction. Whether this is so with oral fat is not known. The question is important because there is debate about whether the type of fat is as important as the quantity of fat in a person's daily diet. Settling this debate will enhance the ability of health care personnel to determine the optimal dietary recommendations.

This study will make use of a high fat diet consisting of vegetable oils high in the 3 main fatty acids in plasma (palmitate, oleate and linoleate). Because large fat loads can cause intestinal discomfort, a feeding tube will be used to bypass the stomach. The 3 oils will be assigned randomly following a base line study with saline 2 weeks prior to the intervention. Our primary endpoint is insulin resistance, which will be measured by a euglycemic, hyperinsulinemic clamp. Secondary measures will include changes in blood pressure and in vascular reactivity as measured by ultrasound after brief occlusion of a forearm vessel. The changes will be compared to baseline and to the other 2 groups.

Eligibility

Ages Eligible for Study:

18 Years to 40 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Lean,healthy adults 18 - 40

No chronic medications (birth control pills allowed)

Weight stable

Normal fasting labs performed at screening

Body mass index ≤ 25 kg/M^2 .

Exclusion Criteria:

Insulin dependent diabetes

Thyroid disease

History of diabetes or heart disease

History of type 2 diabetes in parent or sibling

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01541592

Locations

United States, Minnesota

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

Investigators

Principal Investigator:

Robert Nelson, MD

Mayo Clinic

More Information

No publications provided

Responsible Party:

Robert.H.Nelson, Assistant Professor of Family Medicine and Medicine, Mayo Clinic